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- Title
Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice.
- Authors
Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro
- Abstract
Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. Author Summary: Chagas disease (CD) is a neglected tropical illness caused by the parasite Trypanosoma cruzi (T. cruzi). It is endemic in Latin America and affects 10 million people worldwide. Meningoencephalitis occurs in children with acute CD and in immunosuppressed patients suffering acute CD reactivation. During the chronic phase, cerebral manifestations, including ischemic stroke and cognitive impairment, can also occur. Although microvascular alterations have been implicated in Chagas cardiomyopathy, the main clinical form of the disease, there is a lack of discussion in some studies regarding alterations of the cerebral microcirculation in CD. In the present study, we evaluated the functionality of the cerebral microcirculation in mice infected by T. cruzi. Utilizing an intravital video-microscope, we observed in the brain of infected mice a reduction in the number of perfused capillaries, an increased interaction between inflammatory cells and venules, the presence of microvascular platelet-leukocyte aggregates and alterations in the dilatation capacity of arterioles. Moreover, cerebral oxidative stress was increased in infected animals. We concluded that acute CD induced cerebral microvasculopathy.
- Subjects
CHAGAS' disease; ACUTE diseases; OXIDATIVE stress; MICE; ISCHEMIC stroke; ENDOTHELIUM diseases; PARACOCCIDIOIDOMYCOSIS
- Publication
PLoS Neglected Tropical Diseases, 2014, Vol 8, Issue 7, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002998